Water-Dispersible, Magnetically Recyclable Heterogeneous Cobalt Catalyst for C–C and C–N Cross-Coupling Reactions in Aqueous Media

A cobalt catalyst supported on an iron oxide core, denoted as γ-Fe2O3@PEG@THMAM-Co, has been prepared and characterized by Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray mapping, thermogravimetry differential thermogravimetry, vibrating sample magnetometry, and inductively coupled plasma. Polyhydroxy end groups in the shell make the catalyst particles dispersible in water, allowing Hiyama, Suzuki, and C–N cross-coupling reactions of aryl iodides and bromides. The catalyst could be recovered by magnetic decantation and reused for at least five successive runs with a negligent decrease in its activity or changes in its morphology. Water as a solvent without requiring additives, surfactants, or organic co-solvents, as well as an abundant and low-cost cobalt catalyst combined with facile recovery, low leaching, and scalability, provides an environmentally and economically attractive alternative to established palladium-catalyzed C–C and C–N coupling reactions.


■ INTRODUCTION
−5 Consequently, the development of novel methods for their synthesis continues to be an active research area, 6−8 focusing especially on palladium-based transformations. 9−12 In the past decade, a number of Co-catalyzed systems have been reported for C−C and C−N cross-coupling reactions, 13 such as mTEG-CS-Co-Schiff-base, 14 cobalt-bisoxazolines, 15 a mono (NHC) dicobalt complex [(IPr)(Co 2 )Co(μ−η: 2 η 2 -HCCPh)Co(CO) 3 ], 16 graphene oxide-immobilized cobalt Schiff base complexes (CoASGO), 17 P4VP-CoCl 2 , 18 or Fe 3 O 4 @PEG/Cu−Co. 19espite the economic benefits, applying cobalt compared with palladium catalysts in cross-coupling reactions is still rare.Besides developing cobalt catalysts with high activity, given the toxicity of this metal, it is equally important to establish systems that are recoverable along with low metal leaching and that can be applied under biocompatible conditions. 20ne promising approach to achieve the latter is the heterogenization of catalysts by embedding them into a suitable support.Various organic and mineral materials such as zeolites, 21 polymers, 22 mesoporous materials, 23 etc., have been used for this purpose. 24Especially, magnetic nanoparticles (MNPs) are attractive supports due to their special physical and chemical properties, holding the promise to combine the best of both worlds, i.e., homogeneous and heterogeneous catalysis. 25,26γ-Fe 2 O 3 MNPs are arguably more suitable platforms than other MNPs due to their high resistance against oxidation and their high saturation magnetism while being paramagnetic and thus having a low tendency for agglomeration in the absence of a magnetic field. 27,28On the other hand, from the perspective of sustainable chemistry and development, the use of green solvents in chemical reactions is highly desirable. 29Water has unique advantages compared to conventional organic solvents as it is widely available and abundant, economical and safe, nonvolatile, nonflammable, nontoxic, and non-carcinogenic.However, the performance and selectivity of catalysts supported on MNPs are not high in water, especially when the substrates employed for a reaction have low solubility in the latter. 30Therefore, developing water-dispersible MNPs while maintaining their heterogeneous character for effective recovery is desirable.
Aiming to design a magnetic platform that is waterdispersible, we set out to combine readily available iron oxide MNPs as the cores decorated with a hydrophilic coating that would allow the facile incorporation of catalytically active cobalt nanoparticles.As part of the continued efforts of our research groups to promote green and water-dispersible catalysts, 31,32 we report here a water-dispersible and magnetically recyclable cobalt catalyst using γ-Fe 2 O 3 MNPs modified by PEG (polyethylene glycol) as a hydrophilic platform (Scheme 1) for cross-coupling reactions, including, Suzuki, Hiyama, and C−N couplings in water.
General Procedure for the Suzuki Cross-Coupling Reaction (9a−9q).6 (0.6 mol %, 0.007 g) was added to a mixture of aryl halide (1.0 mmol), phenylboronic acid (1.2 mmol), and K 2 CO 3 (2.0 mmol) in water (4 mL) under stirring and heated for the indicated time at 80 °C, monitoring the progress of the reaction by thin layer chromatography (TLC) until completion.The nanocatalyst was separated by an external magnet and washed with ethyl acetate (3 × 3 mL).The aqueous phase was extracted with ethyl acetate (3 × 5 mL), and the combined organic layers were dried over anhydrous Na 2 SO 4 .After evaporation of the solvent under reduced pressure, the crude product was purified by column chromatography on silica (eluent: n-hexane/EtOAc 8:2) to obtain products 9a−9q.
General Procedure for the Hiyama Cross-Coupling Reaction (11a−11m).6 (0.6 mol %, 0.007 g) was added to a mixture of aryl halide (1.0 mmol), NaOH (2.0 mmol), and triethoxyphenylsilane (1.5 mmol) in water (4 mL) under stirring and heated for the indicated time at 80 °C, monitoring the progress of the reaction by TLC until completion.The nanocatalyst was separated by an external magnet and washed with ethyl acetate (3 × 3 mL).The aqueous phase was extracted with ethyl acetate (3 × 5 mL), and the combined organic layers were dried over anhydrous Na 2 SO 4 .After evaporation of the solvent under reduced pressure, the crude product was purified by column chromatography on silica (eluent: n-hexane/EtOAc.
Scanning electron microscopy (SEM) investigations were also performed to study the surface and cross-sectional morphology during the preparation of 6 (Figure 3a−f), showing homogeneity, spherical morphology, and uniform size distribution of the materials in all of the steps.In addition, the morphology of 6 was analyzed by transmission electron microscopy (TEM) (Figure 4), showing a small, spherical structure without significant agglomeration.
Energy-dispersive X-ray (EDX) analysis confirmed that 6 contains Co, N, C, O, Si, Cl, and Fe (Figure 5).EDX elemental mapping also shows all expected elements, including Fe, N, C, Si, Co, O, and Cl but, moreover, proved that Co is homogeneously distributed on the γ-Fe 2 O 3 @PEG platform (Figure 6), which is especially relevant for high catalytic activity.Important for the subsequent catalytic cross-coupling reactions, ICP-OES analysis showed no presence of copper, nickel, or palladium within the detection limit (<10 ppm).
Thermogravimetry analysis (TGA) of 6 at a heating rate of 10 °C min −1 in the temperature range of 25−800 °C under a nitrogen atmosphere (Figure 7) showed weight loss at five stages totaling 18.7%, giving credit to the high thermal stability of γ-Fe 2 O 3 @PEG@THMAM-Co 6.The initially trapped water in the crystalline structure of the Co complex 6 is likely to be removed (2.1 W % loss, ∼120 °C), followed by decomposition of the organic linker materials grafted onto the surface of γ-Fe 2 O 3 in the regions of 278 and 509 °C (3.5 and 7.5 W % loss) (Figure 7).At even higher temperatures (650 and 800 °C), the observed weight loss (2.9 and 2.7 W %) is most likely related to the removal of PEG as well as of mineral impurities in γ-Fe 2 O 3 1 (Figure 7).
The magnetic properties of γ-Fe 2 O 3 MNPs 1 and γ-Fe 2 O 3 @ PEG@THMAM-Co 6 were evaluated by using vibrating sample magnetometry analysis (VSM) at 25 °C (Figure 8).According to the VSM results, the magnetization for γ-Fe 2 O 3 MNPs was found to be 55 emu g −1 , which dropped to 31 emu g −1 for γ-Fe 2 O 3 @PEG@THMAM-Co 6 (Figure 8), being in line with the successful functionalization of γ-Fe 2 O 3 MNPs 1. Finally, a loading of 0.95 mmol of Co/g of 6 was determined by ICP-OES analysis.
Evaluation of the Catalytic Activity of γ-Fe 2 O 3 @PEG@ THMAM-Co MNPs 6.Given the hydrophilic properties of γ-Fe 2 O 3 @PEG@THMAM-Co 6 (Figure 9), we evaluated the prepared material for its catalytic activity in water.−46 Suzuki and Hiyama Cross-Coupling Reactions.Catalyst 6 with a remarkable low loading of only 0.6 mol % showed high activity for Suzuki (Table 1) and Hiyama (Table 2) crosscoupling reactions of aryl iodides and bromides.Under optimized conditions (see the Supporting Information for screening details, Tables S1 and S2), electronically and sterically varied aryl iodides and aryl bromides were successfully coupled with a representative set of phenylboronic acids or triethoxyphenylsilane.While aryl iodides (70−95%) gave generally higher yields than aryl bromides (60−86%), aryl chlorides proved to be unreactive in the title transformations.
C−N Coupling Reactions.Likewise, the performance of 6 was evaluated for the coupling of phenylboronic acids and amines (see the Supporting Information for screening details, Table S3).An increased catalyst loading (3 mol %) was necessary compared to that in the previously discussed coupling reactions (vide supra) to achieve high yields (72− 90%).
Recyclability Study.Recyclability of 6 was evaluated for all three reaction types previously investigated, i.e., Suzuki, Hiyama, and C−N couplings, for 5 consecutive runs each (Table 4), giving consistent high yields with only a minimal decrease (≤5%) in activity.Capitalizing on the iron oxide core of 6, recovery of the catalyst by application of an external magnet was facile and quantitative.
FT−IR analysis was performed for reisolated 6 after five runs for all reaction types (Figure 10a−d), demonstrating the stability of the catalyst over time.
The comparison of TEM and SEM images of fresh and used catalysts after 5 runs in Suzuki coupling also showed no significant changes in particle size and morphology (Figure 11a,b).However, some agglomeration can be seen in the TEM image that is associated with dipole−dipole interactions of MNPs (Figures 11a,b, cf.Figures 3f and 4).
ICP analysis revealed low leaching of cobalt between ≤1 wt % for each run based on the initial cobalt content (0.6 mol % in Suzuki and Hiyama couplings and 3 mol % in C−Ncoupling) used (Figure 12).

■ CONCLUSIONS
In conclusion, we have developed an efficient protocol using water-dispersible, magnetically retrievable, and reusable cobalt catalyst γ-Fe 2 O 3 @PEG@THMAM-Co 6 in water for Suzuki, Hiyama, and C−N-couplings of aryl iodides and bromides, offering an alternative to the corresponding palladiumcatalyzed transformations.While Suzuki couplings for aryl bromides and aryl iodides with "homeopathic amounts of palladium nanoparticles" (0.3−50 ppm) have been reported, it should be noted that taking the cost of palladium vs cobalt into account, the amount of cobalt used here would be equivalent to catalysis with 3 ppm palladium.

Figure 12 .
Figure 12.Recycling and determination of the amount of metal leaching of the catalyst during five runs under optimal reaction conditions (cf.Table 4): (a) Suzuki coupling for 9a.(b) Hiyama reaction for 11a.(c) C−N coupling for 13b.

Table 3 .
C−N Coupling Reactions of Different Amines with Phenylboronic Acid Derivatives Catalyzed by γ-Fe 2 O 3 @ PEG@THMAM-Co 6 a b Isolated yield.